DESCRIPTION (Investigator's Abstract): We will examine the efficacy and toxicity of orally administered interferon-alpha (IFN-alpha) in decreasing new MRI (Magnetic Resonance Imaging) brain lesions and secretion of IL-2, IFN-gamma, IL-4, IL-10 and TGF-beta in patients with relapsing-remitting multiple sclerosis (RR-MS). A recent study of parenterally administered human recombinant hrIFN-beta,1b in RR-MS suggest that 8 million units of hrIFN-beta,1b s.c. every other day can decrease relapses by 30 percent, decrease brain inflammation and the frequency of active lesions as accessed by serial quantitative MRI. However 40 percent of IFN-beta,1b treated patients generated neutralizing antibodies that may be more frequently found in those patients who appear to lose both clinical benefits and MRI defined responses. We have shown that the oral administration of type-1 IFNs can prevent acute experimental autoimmune encephalomyelitis (EAE), suppress relapses in chronic relapsing EAE, decrease mitogen or antigen induced IFN-gamma secretion, and that oral administration is more effective in preventing acute or relapse attacks than equivalent doses of s.c. IFN-alpha in these animal models of MS. Adoptive transfer of activated CD4+ and CD8+ T cells from IFN-alpha fed donor animals inhibits actively induced EAE in recipients by increased IL-4 and IL-10. Recent data from our group demonstrates that normal human volunteer subjects ingesting 30,000 units of human recombinant IFN-alpha produce less IFN-gamma via the CD3 mediated pathway, subjects with early RRMS ingesting IFN-alpha demonstrate decreased Con A-mediated proliferation, decreased IL-2, IFN-gamma, TGF-beta and IL-10 secretion, and decreased soluble serum ICAM-1 levels. In addition, ingested IFN-alpha increased relative IFN-induced Mx mRNA levels in mouse splenocytes and human peripheral mononuclear cells, thereby allowing an investigation of the specific cell target responsible for immunomodulation induced by ingested IFN. This treatment is unlikely to be abrogated by the presence or induction of circulating neutralizing IFN antibodies seen in parenteral IFN-beta. Thus, oral IFN-alpha therapy a unique opportunity to mimic the cytokine profile of MS in clinical remission. Thirty patients with early RR-MS screened for eligibility by at least one contrast enhancing lesion on a single pre-entry scan, will be studied in a Phase II design trial of alternate day orally administered placebo, or hrIFN-alpha at 10,000, or 30,000 units with monthly brain gadolinium enhanced T1 and multi-echo high resolution unenhanced MRI scans and monitoring of cytokine and soluble adhesion molecule levels for up to 0.75 years. Outcome measures will be decreases in the number of active scans using automated quantitative lesional assessment of MRI enhancements. The effect of ingested IFN-alpha treatment on soluble serum intercellular molecules level and induction of Type-1 IFN-specific Mx mRNA will also be assessed. Ingested IFN-alpha may provide superior efficacy and safety in comparison to parenteral administered Type-1 IFNs in RR-MS and other autoimmune diseases.